GeneBe

rs864309538

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_001271.4(CHD2):​c.1808delA​(p.Lys603ArgfsTer20) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CHD2
NM_001271.4 frameshift, splice_region

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.32

Publications

0 publications found
Variant links:
Genes affected
CHD2 (HGNC:1917): (chromodomain helicase DNA binding protein 2) The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
CHD2 Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • developmental and epileptic encephalopathy 94
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • Lennox-Gastaut syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • myoclonic-astatic epilepsy
    Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHD2NM_001271.4 linkc.1808delA p.Lys603ArgfsTer20 frameshift_variant, splice_region_variant Exon 15 of 39 ENST00000394196.9 NP_001262.3 O14647-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHD2ENST00000394196.9 linkc.1808delA p.Lys603ArgfsTer20 frameshift_variant, splice_region_variant Exon 15 of 39 5 NM_001271.4 ENSP00000377747.4 O14647-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1431612
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
712062
African (AFR)
AF:
0.00
AC:
0
AN:
31692
American (AMR)
AF:
0.00
AC:
0
AN:
38988
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25418
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38136
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81166
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52680
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5722
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1098618
Other (OTH)
AF:
0.00
AC:
0
AN:
59192
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
9.3
Mutation Taster
=0/200
disease causing (fs/PTC)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs864309538; hg19: chr15-93498739; API